Post-synaptic Function Flashcards
What is a dendritic spine
A small membranous protrusion from a neurons dendrite that typically receives input from a single axon at the synapse (postsynaptic receivers)
- have a spine neck and spine head
What is the role of a dendritic spine
Serves as a storage site for synaptic strength and help transmit electrical signals to the neurons cell body
Provide functional compartmentalisation(ionic and biochemical changes are restricted just to the activated synapse)
What is input specificity
Synaptic changes occur specifically at the synapses that are activated
What is post-synaptic density
Neurotransmitter receptors are in the PSD, anchored and regulated by a network of proteins
-Core
-Pallium
Outline excitatory post-synaptic potential (EPSP)
Net movement of cations into the postsynaptic cell generates an EPSP, which depolarises the membrane potential
Outline inhibitory post-synaptic potential (IPSP)
Net movement of anions into the postsynaptic cell or cations out of the postsynaptic cell generates an IPSP which hyperpolarises the membrane potential (Vm)
What is L-glutamate
Non-esssential amino acid, synthesised from glutamine by the enzyme glutaminase
Most abundant excitatory neurotransmitter in the NS
(90% of synapses in the brain signal using glutamate)
What are the key properties that indicate L-glutamate is a neurotransmitter
-stored in synaptic vesicles (VGLUT transporters transfer glutamate from the cytoskeleton into vesicles)
-Ca dependent release
-specific protein targets (receptors)- ionic glutamate receptors, metabotropic glutamate receptors
-mechanism for rapid removal of transmitter from synapse- glutamate transporters on pre and postsynaptic neuron terminals and on astrocytes
-process for glutamate synthesis within presynaptic terminals
What are the ionotropic glutamate receptor subtypes?
-AMPA
-NMDA
-Kainate
Most gluatmatergc synapses have both AMPA and NMDA classes of iGlu receptor.
What are the glutamate metabotropic receptor subtypes?
Group I,II,III
Outline AMPA receptors
-do ‘most of the business’ of excitatory synaptic communication
-permeable to Na and K ions
-do not usually pass Ca ions
Outline NMDA receptors
-activated under ‘special conditions’
-permeable to Ca ions, as well as Na and K
-this Ca flux allows local biochemical changes to be triggered when NMDA receptors are activated
What is the general structure of a single ionotropic glutamate receptor
Less complex, 4 transmembrane domains( TM1-4)
N terminus and ligand binding domain exists in extracellular domain
C terminus exists in intracellular domain
How do AMPA and NMDA receptors work together?
Both have tetrameric asssemblies (contain 4 subunits)
NMDA receptors are always heterotetramers (contain at least two types of subunit) AMPA are usually
Outline the structure of AMPA receptors
-Mixtures of GluA1-4 subunits
-most receptors contain a GluA2 which makes the pore impermeable to Ca
-permeable to Na and K ions and produce a high amplitude short-lived EPSP
Outline the structure of NMDA receptors
-mixtures of GluN1 and GluN2 subunits
-Ca permeable with a crucial voltage-dependent Mg block
How is fast synaptic transmission mediated by ionotropic receptors?
Mg blocks NMDA, Na enters AMPA receptors on postsynaptic dendrite
AMPA receptor antagonists can block EPSP
Outline the Mg block of NMDA receptors
Mg block of NMDA receptor channels is voltage dependent
At a membrane voltage of around -35mv (depolarised potential), the Mg block of the NMDA receptor channel is removed
This means that inward current through NMDARs is neurotransmitter gated and voltage dependent
What are the physiological role of NMDA receptors?
Mediate slow-rising, long-lasting excitatory postsynaptic currents via Na and Ca entry through the channel pore
The Ca flux enables local biochemical changes
What is the main inhibitory neurotransmitter in the brain
GABA
What are the key properties that indicate GABA as a neurotransmitter
-stored in synaptic vesicles
-Ca dependent release
-specific protein targets(receptors), ionotropic, metabotropic
-mechanism for rapid removal of transmitter from synapse - GABA transporters on pre and post-synaptic neuron terminals and on astrocytes
-process for GABA synthesis on pre and postsynaptic-synaptic neurons
What is a key difference between GABAergic and glutamatergic synapses
GABAergic synapses do not typically form onto dendritic synapses
Outline GABAa receptors
-ionotropic
-pentameric (made up of 5 subunits around a central pore
-each subunits contains 4 transmembrane (TM) domains- TM2 forms the channel pore
-two molecules of GABA to open- bind between alpha and beta subunits
-negatively charged chloride ions flow along their electrochemical gradient into the cell- hyperpolarises the cell
How do GABAa receptors mediate fast inhibitory synaptic transmission?
Phasic inhibition hyperpolarises the postsynaptic cell- generates IPSP
Chloride ions enter GABAaR on the postsynaptic dendrite
Most GABAergic synapses do not form on dendritic spines-dendrite or soma
Outline GABAb receptors
-metabotropic
-heterodimeric G-protein coupled receptors
-functional receptor compromises two 7-transmembrane subunits:
GABAb1 subunits- binds to GABA
GABAb2 subunits- required for G-protein signalling (Gio pathway coupled)
How do GABAb receptors mediate slow inhibitory synaptic transmission
GABAa receptors are blocked
Beta gamma subunit interacts with potassium ions- eflux of potassium ions creates a hyper polarising potential
Outline the coactivation of GABAaRs and GABAbRs
Produces long-lasting biphasic IPSPs
Fast component mediated by GABAa receptors
Secondary slow mediated by GABAb receptors
Where are GABAb receptors commonly found
On presynaptic terminal
Autoreceptor
The presence of GABAb receptors can lead to a form of paired pulse depression
Outline an autoreceptor
A receptor found on a presynaptic terminal that is activated by the neurotransmitter released by that same synapse.
How is GABAb receptors mediated for suppression of inhibition
-GABAb receptors couple to Gi/o G-protein signalling
-activation of presynaptic GABAb receptors inhibits presynaptic voltage-gated Ca channels (decreases their probability of opening)
-this restricts Ca entry into the presynaptic terminal
-therefore, the 2nd (conditioned) stimulus results in reduced Ca dependent exocytosis; less GABA is released
